The H-2 major histocompatibility complex of the mouse controls a variety of functions which are important to research on transplantation, viral oncogenesis, disease resistance, and fundamental genetic and immunologic mechanisms. In this context it is also an important model for the HLA complex in man. The broad, long-range objective of the proposed research is the elucidation of the number, organization, function and regulation of the multiple genes of the H-2 complex which control these diverse traits, especially the genes of the I region that control specific immune responses, lymphoid cell interactions, the mixed leukocyte reaction (MLR), and the Ia lymphocyte antigens. Two general aspects of the H-2 complex are under investigation: 1) Genetic organization--Large scale screening for recombination and mutation within the H-2complex is in progress. All H-2 variants detected will be extensively characterized for H-2-associated traits, in order to separate, identify and map the controlling genes. Particular attention will be given to analysis of I region traits. 2) Genetic function-- To elucidate the functions of certain specific genes, more intensive studies are being carried out. The Ss proteins will be analyzed for their biochemical properties, hormonal regulation, and complement (C4) activity. The relationship of Ia antigens to other I region traits or immune functions (MLR, cellular cooperation, in vitro PFC response, mitogen stimulation) is being probed by analyses of capacity of anti-Ia sera to inhibit these functions. The H-2G antigen will be analyzed biochemically and serologically. A search for additional serological systems in the H-2 complex will also be made. BIBLIOGRAPHIC REFERENCES: Zinkernagel, R. M., M. B. C. Dunlop, R. V. Blanden, P. C. Doherty and D. C. Shreffler. H-2 Compatibility Requirement for Virus-Specific T-Cell-Mediated Cytolysis. J. Exp. Med. 144: 519, 1976. Hoffsten, P. E., C. Hill and D. C. Shreffler. Glomerular Deposition of Ss Protein in Murine Immune Complex Glomerulonephritis. Clinical Immunology and Immunopathology 6: 47, 1976.